Without limiting the scope of the invention, this background describes particles capable of directly binding a wide variety of bio-molecules with and without the use of hybridizing reagents. One factor that currently affects the usefulness of many diagnostics is the rapid, selective, and sensitive detection of biochemical substances, e.g., proteins, metabolites, nucleic acids, biological compounds, etc. Another factor is that it is often necessary to identify and differentiate between a large number of biochemical constituents in complex samples.
Bioprobes are receiving increased emphasis by researchers since they overcome many of these limitations. Generally, these assays use fluorescent or chemiluminescent labels which have certain limitations, e.g., spectral specificity. For example, one spectroscopic technique, Raman spectroscopy, is a phenomenon observed in the scattering of light as it passes through a material medium so that the light experiences a change in frequency and a random alteration in phase. In so doing the scattered photons have the same energy (frequency) and, therefore, wavelength, as the incident photons; however, a small fraction of light is scattered at optical frequencies different from the frequency of the incident photons, i.e., the Raman effect. Raman scattering can occur with a change in vibrational, rotational or electronic energy of a molecule. In addition, Raman spectroscopy is complementary to fluorescence and has been used as an analytical tool; however, low sensitivity historically has limited its applications.
Recently, a technique associated with this phenomenon called surface-enhanced Raman scattering (SERS) spectroscopy has been used for molecules adsorbed on microstructures of metal surfaces. This enhancement embodies a microstructured metal surface scattering process which increases the intrinsically weak normal Raman scattering due to a combination of several electromagnetic and chemical effects between the molecules adsorbed on the metal surface and the metal surface itself.